Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Non-human information

 

In vitro data

The key studies are considered to be a bacterial mutation assay (Victorin & Stahlberg, 1988) and a mammalian cell cytogenetic assay (Riley, 1996).  These are two recognised core assay types for investigating mutation in vitro.

Ethylene was tested in an Ames plate assay modified to allow exposure to a gaseous material (Victorin & Stahlberg, 1988). Salmonella typhimurium strain TA100 was selected as a strain sensitive to base pair substitution mutations since these were considered the most likely to occur from a simple alkene rather than possible frameshift mutations. Exposures were carried out both with and without auxiliary metabolic activation (S9). A range of doses was used from 0.5 to 20% atmospheres. Ethylene was negative in this assay.

Ethylene was tested for cytogenetic activity in CHO cells both in the presence and absence of S9. A range of doses up to approximately 275 µg/ml (approximately 10mM) was used, with exposure for 3 hours, under modified conditions appropriate for a gaseous material. Ethylene was negative in this assay.

There are additional reports of mutation data using further strains of Salmonella and E coli that support the above conclusion of no mutagenic activity (Agrochemical Draft Assessment Report (DAR), fourth stage review under Council Directive 91/414/EEC, 2008).

 

In vivo data

The key studies are considered to be bone marrow micronucleus studies in the mouse and rat (Vergnes et al, 1994; Dow 2010). This is a recognised core assay type for investigating mutation in vivo.

Ethylene was studied in a rodent bone marrow micronucleus assay in male B6C3F1 mice and Fischer 344 rats exposed by inhalation to atmospheres of 0, 39, 966, 2995 ppm for 6 hours/day, 5 days/week for 4 weeks.  Samples of bone marrow cells were taken for cytogenetic analysis at 24 hours after the final exposure. No significant increases in micronucleated polychromatic erythrocytes were found (Vergnes et al 1994). 

In another bone marrow micronucleus assay, Dow (2010) exposed male and female F344/DuCrl rats to ethylene at 0, 302, 1001, 3024, or 10,134 ppm for 6 hours/day, 5 days/week for 13 weeks. Blood samples were taken and examined 18 hours after exposure at day 5 and day 90 of the study. Bone marrow samples were taken after 90 days of the study. No significant increases in micronucleated erythrocytes were found. Ethylene gave a negative result in these two cytogenetic studies.

Ethylene was also negative in an assay examining for HPRT gene mutation in splenic T cells in male F344 rats and B6C3F1 mice exposed by inhalation to 0, 39, 966 and 2992 ppm ethylene for 6 hours/day, 5 days/week for 4 weeks (Walker et al 2000).

 

Human information

There is no information indicating any adverse effects of ethylene. 

 

Summary

Ethylene has been examined for mutagenicity both in vitro and in vivo in a range of recognised core assay types. It has shown negative results for mutagenicity both in vitro and in vivo. It is concluded that the available data indicate that ethylene has no significant genotoxicity.


Short description of key information:
Review of a comprehensive database indicates that ethylene is not genotoxic

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Ethylene does not warrant classification for genotoxicity under Dir 67/548/EEC or GHS/CLP.